The original ending for the series, as proposed by the writers, was for Angela and Tony to get married. ABC executives, however, balked at this ending and were supported by Tony Danza, who was against having Tony and Angela get married in the series finale. So the series ended with Tony and Angela breaking up but with Tony appearing on Angela's doorstep to apply for the housekeeper job in a scene that is almost identical to the opening scene in the pilot episode.

Although they both play family matriarchs, neither Judith Light nor Katherine Helmond have any children in real life. Furthermore, Judith Light is still married to the same man, not like her character who was a divorcée.

At the end of season three, the producers of the show decided to spin-off the Mona character into her own series. As a result, the season ended with a two-part episode where Mona moves away in order to run a hotel with her brother while Tony and Samantha move into Mona's loft apartment. However, due to the fear that Mona's departure might harm the success of the show, the plans for the spin-off were squashed by ABC executives and a tag sequence was added at the end of the two-parter which featured Mona returning home and Tony and Samantha moving back into Angela's house.

The pilot episode was filmed in October 1983 but held back from ABC executives for nearly a year due to the producers of the series being afraid that the show would be rejected by ABC executives if pitched as a mid-season replacement series.

Episode #115, (Living Dolls) was never shown during the series' original prime time run and instead premiered when "Who's the Boss" first entered syndication. The episode, which was meant to be a pilot for a new ABC series Living Dolls (1989), was pulled from the schedule, due to last minute casting changes to the series. Several months later, a second episode (episode #123, "Life's A Ditch") was filmed to serve as a pilot for "Living Dolls", which aired on the same night "Living Dolls" finally premiered.

German network RTL showed a German version of the show called Ein Job für's Leben (1993) ("A Life-Time Job"). The scripts and every single joke of the original's 1984-1985 season were translated, but it was canceled after one season. "Ein Job für's Leben" was preceded by a British version, The Upper Hand (1990), starring Honor Blackman, which fared somewhat better despite also being a direct translation instead of an adaptation or reinvention. It was canceled in 1996.

ABC originally planned to cancel the show at the end of the seventh season but the producers were able to convince the network to renew the show for an eighth season. As part of the deal to renew the show (and to revive fan interest) it was decided to base the entire eight season around Tony and Angela finally becoming a couple. When ratings for the eighth season failed to increase, the show was cancelled.

Mona was originally intended to be Angela's older sister, but producers were unable to find an age appropriate actress they liked for the part. As a result, they decided to redevelop Mona to be Angela's mother instead.